title: P-selectin glycoprotein ligand-1 deficiency augments G-CSF induced myeloid cell mobilization.
abstract: The effect of granulocyte colony-stimulating factor (G-CSF) was investigated in P-selectin glycoprotein ligand-1 (PSGL-1) deficient (PSGL-1(-/-)) and wild-type (PSGL-1(+/+)) mice to establish the role of this mucin in myeloid cell mobilization. G-CSF activates tissue proteases that cleave adhesion molecules, thus enhances the mobilization of myeloid cells and haematopoietic stem cells. Cytopenia was induced with a single dose of cyclophosphamide. In PSGL-1(-/-) animals, we observed a delayed extravasation of mature myeloid cells from the peripheral vessels into the tissue compartments and their faster mobilization from the bone marrow. Subsequently, animals received G-CSF twice a day for 4 days. Neutrophil and monocyte counts increased upon completion of G-CSF treatment and both values were significantly higher in PSGL-1(-/-) mice; 47.7 versus 28.3 G/l for neutrophils and 4.1 versus 2.0 G/l for monocytes. The ratio of atypical myeloid cells was also elevated. Analyzing the causes of the above differences, we identified a 4-fold increase in the colony-forming unit (CFU-GM) counts of the peripheral blood in PSGL-1(-/-) mice, compared to wild-type animals. A significantly elevated number of CFU-GM was detected also in the femurs of PSGL-1(-/-) mice, 4 and 5 days after cyclophosphamide treatment and these values paralleled with the elevation of CD34+/CD117+ stem cell counts in the peripheral blood. Our data suggest, that in the absence of PSGL-1, G-CSF was more potent in elevating absolute myeloid cell numbers by acting on cell release from the bone marrow, maturation from circulating precursor cells in the peripheral blood and prolonged retainment in the circulation.
authors.affiliation: Department of Laboratory Medicine, Medical and Health Science Center, University of Debrecen, Nagyerdei krt 98, 4032, Debrecen, Hungary.
authors.forename: Kornél
authors.initials: K
authors.lastname: Miszti-Blasius
authors.forename: Szabolcs
authors.initials: S
authors.lastname: Felszeghy
authors.forename: Csongor
authors.initials: C
authors.lastname: Kiss
authors.forename: Ilona
authors.initials: I
authors.lastname: Benkő
authors.forename: Krisztina
authors.initials: K
authors.lastname: Géresi
authors.forename: Attila
authors.initials: A
authors.lastname: Megyeri
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Hevessy
authors.forename: János
authors.initials: J
authors.lastname: Kappelmayer
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002452:Cell Count; D003520:Cyclophosphamide / Q000494:pharmacology; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000172:deficiency* / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019653:Myeloablative Agonists / Q000494:pharmacology; D022423:Myeloid Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects
chemical_list: D018952:Antigens, CD34; D008562:Membrane Glycoproteins; D019653:Myeloablative Agonists; C084882:P-selectin ligand protein; D016179:Granulocyte Colony-Stimulating Factor; D003520:Cyclophosphamide; D019009:Proto-Oncogene Proteins c-kit